2- Substituted thiophenes, irradiation

The stable Dewar thiophene (68) is obtained by irradiation of 2,3,4,5-tetrakis(trifluoromethyl)thiophene (Scheme 150) (72ClC272l). Dewar thiophenes are proposed as intermediates in the photochemical isomerizations of substituted thiophenes (Scheme 17). 

Wynberg has discovered the most interesting reaction in the photochemical reactivity of thienyl derivatives. The irradiation of 2-substituted thiophenes gave the corresponding 3-substituted derivatives (Scheme 17). 

Several further experimental results lend support to the mechanisms postulated to explain the formation of the photoproducts. Thus irradiation of thiophene and substituted thiophenes in the presence of -propylamine leads to pyrroles, presumably via cyclopro-penylthiocarbonyl, or Dewar thiophene, intermediates (75T785). An extremely interesting development is the isolation of l,2,3,4-tetrakis(trifluoromethyl)-5-thiabicyclo[2.1.0]pent-2-ene, or perfluoro(tetramethyl Dewar thiophene) (2) by vapor-phase irradiation of perfluorotetramethylthiophene (81ACR76) the yield is about 58%. The half-life of thermal rearomatization of (2) at 160 °C is 5.1 h. The fluxional behaviour of the Dewar thiophene... 

Kiryanov, A.A., Sampson, R and Seed, A.J., Synthesis of 2-alkoxy-substituted thiophenes, 1,3-thiazoles, and related S-heterocycles via LawessoiTs reagent-mediated cyclization under microwave irradiation applications for liquid crystal synthesis, /. Org. Chem., 2001, 66, 7925-7929. 

The photoisomerization of 2-substituted thiophenes into the corresponding 3-substituted derivatives is a common pathway observed for both 2-aryl and 2-alkylthiophenes [4]. However, for synthetic applications, a significant example can be recognized in the photoisomerization of 2-arylthiophenes 33 into the corresponding 3-aryl derivatives 34 by the large-scale irradiation in Et20 with a high-pressure Hg lamp (Scheme 12.10) [28]. 

The photochemical heteroarylation of thiophenes has been further exemplified. Irradiation of 4,5-diiodopyrrole 2-carbaldehyde with thiophene or 2-chlorothiophene leads to the pyrrole-substituted thiophenes in high yield (Equation 18) <1997J(P1)2369>. Similarly, irradiation of 4(5)-nitro-2-iodoimidazole in the presence of thiophene or 2-chlorothiophene produces the imidazole-substituted thiophenes 54 in good yields <1998J(P1)271>. 

The light-induced rearrangement of 2-phenyl- to 3-phenyl-thiophene may occur by a similar mechanism an equilibrium between the bicyclic intermediate (26) and the cyclopro-penylthioaldehyde (27) has been suggested (Scheme 2). The formation of IV-substituted pyrroles on irradiation of either furans or thiophenes in the presence of a primary amine supports this suggestion (Scheme 3). Irradiation of 2-phenylselenophene yields, in addition to 3-phenylselenophene, the enyne PhC=C—CH=CH2 and selenium. Photolysis of 2-phenyltellurophene furnishes solely the enyne and tellurium (76JOM(108)183). 

Methylthiophene is metallated in the 5-position whereas 3-methoxy-, 3-methylthio-, 3-carboxy- and 3-bromo-thiophenes are metallated in the 2-position (80TL5051). Lithiation of tricarbonyl(i7 -N-protected indole)chromium complexes occurs initially at C-2. If this position is trimethylsilylated, subsequent lithiation is at C-7 with minor amounts at C-4 (81CC1260). Tricarbonyl(Tj -l-triisopropylsilylindole)chromium(0) is selectively lithiated at C-4 by n-butyllithium-TMEDA. This offers an attractive intermediate for the preparation of 4-substituted indoles by reaction with electrophiles and deprotection by irradiation (82CC467). 

Despite that the thiophene ring is considered as a bioisoster of the benzene ring, the synthesis and chemistry of thiophene analogs of heterocycles with therapeutic interest remain poorly studied. One of the most recent examples concerns the synthesis of new substituted thioisatoic anhydrides (6 and 7-arylthieno[3,2-d] [1,3]oxazine-2,4-diones), which were prepared on a large scale under microwave irradiation conditions. A small library of thiophene ureidoacids was easily performed using a Normatron microwave reactor (500 W) with high yields and good purity [4,5] (Scheme 4). 

The [2 + 2] photodimerization of a, j8-unsaturated sulfones is correctly viewed as a photoreaction of alkenes, rather than the sulfone group, and this aspect has been reviewed recently by Reid, as part of a wider survey of the photoreaction of O- and S-heterocycles. The topic continues to attract considerable interest and a few recent examples, as well as some synthetic applications, will be discussed here. Much of the photodimerization work has been carried out on the benzo[fc]thiophene (thianaphthene) 1,1-dioxide system. For example. Porter and coworkers have shown that both 3-carboxybenzo[i]thiophene 1,1-dioxide (65) and its methyl ester give only the head-to-head (hth), anti dimer (66) on irradiation in ethanol. In a rather unusual finding for such systems, the same dimer was obtained on thermal dimerization of 65. Similar findings for a much wider variety of 3-substituted benzo[fi]thiophene 1,1-dioxides have been reported more recently by Geneste and coworkers . In the 2-substituted analogs, the hth dimer is accompanied by some of the head-to-tail (htt), anti dimer. The formation of the major dimer appears to proceed by way of an excited triplet and the regiochemistry observed is in accord with frontier MO theory. 

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